Dege N

References (4)

Title : Development of new benzil-hydrazone derivatives as anticholinesterase inhibitors: synthesis, X-ray analysis, DFT study and in vitro\/in silico evaluation - Tabbiche_2024_J.Biomol.Struct.Dyn__1
Author(s) : Tabbiche A , Bouchama A , Fadli K , Ahmad B , Kumar N , Chiter C , Yahiaoui M , Zaidi F , Boudjemaa K , Dege N , Djedouani A , Chafai N
Ref : J Biomol Struct Dyn , :1 , 2024
Abstract : Alzheimer's disease (AD) is a complex neurodegenerative disorder affecting the central nervous system. Current drugs for AD have limited effectiveness and often come with side effects. Consequently, there is a pressing need to develop new, safe, and more effective treatments for Alzheimer's disease. In this work, two novel benzil-hydrazone compounds, abbreviated 2-ClMHB and 2-ClBHB, were synthesized for the first time by refluxing the benzil with 2-Chloro phenyl hydrazine and they have been tested for their in vitro anti-cholinesterase activities and in silico acetyl and butyryl enzymes inhibition. The resulting products were characterized using UV-Vis and IR spectroscopy, while the single-crystal X-ray diffraction investigation was successful in establishing the structures of these compounds. DFT calculations have been successfully made to correlate the experimental data. According to biological studies, the synthesized hydrazones significantly inhibited both butyrylcholinesterase (2-ClMHB: 20.95 +/- 1.29 microM and 2-ClBHB: 31.21 +/- 1.50 microM) and acetylcholinesterase (2-ClMHB: 21.80 +/- 1.10 microM and 2-ClBHB: 10.38 +/- 1.27 microM). Moreover, molecular docking was also employed to locate the molecule with the optimum interaction and stability as well as to explain the experimental findings. The compound's dynamic nature, binding interaction, and protein-ligand stability were investigated using molecular dynamics (MD) simulations. Analyzing parameters such as RMSD and RMSF indicated that the compound remained stable throughout the 100 ns MD simulation. Finally, the drugs displayed high oral bioavailability, as per projected ADME and pharmacokinetic parameters.Communicated by Ramaswamy H. Sarma.
ESTHER : Tabbiche_2024_J.Biomol.Struct.Dyn__1
PubMedSearch : Tabbiche_2024_J.Biomol.Struct.Dyn__1
PubMedID: 38193889

Title : Experimental and Theoretical Biological Probing of Schiff Bases as Esterase Inhibitors: Structural, Spectral and Molecular Insights - Raza_2023_Molecules_28_5703
Author(s) : Raza MA , Mumtaz MW , Ozturk S , Latif M , Aisha , Ashraf A , Dege N , Dogan OE , Agar E , Rehman SU , Noor A
Ref : Molecules , 28 :5703 , 2023
Abstract : The present study was designed to evaluate the in vitro and in silico potential of the Schiff bases (Z)-4-ethoxy-N-((5-nitrothiophen-2-yl)methylene)benzenamine (1) and (Z)-2,4-diiodo-6-((2-methyl-3-nitrophenylimino)methyl)phenol (2). These Schiff bases were synthesized according to a reported method using ethanol as a solvent, and each reaction was monitored on a TLC until completion of the reaction. The structures of both compounds were elucidated using spectroscopic techniques such as UV-Vis, FTIR, (1)H NMR and (13)C NMR. Molecular structure was determined using single-crystal XRD, which revealed that compounds 1 and 2 were monoclinic and triclinic, respectively. Hirshfeld surface analysis (HS) and 2D fingerprint plots were used to determine the intermolecular interactions along the contact contribution in the crystalline molecules. The structures of both compounds were optimized through a hybrid functional method B3LYP using the 6-31G(d,p) basis set, and various structural parameters were studied. The experimental and theoretical parameters (bond angle and bond length) of the compounds were compared with each other and are in close agreement. The in vitro esterase potential of the synthesized compounds was checked using a spectrophotometric model, while in silico molecular docking studies were performed with AutoDock against two enzymes of the esterase family. The docking studies and the in vitro assessment predicted that such molecules could be used as enzyme inhibitors against the tested enzymes: acetylcholine esterase (AChE) and butyrylcholine esterase (BChE).
ESTHER : Raza_2023_Molecules_28_5703
PubMedSearch : Raza_2023_Molecules_28_5703
PubMedID: 37570673

Title : Synthesis, solid state self-assembly driven by antiparallel Pi-Pi stacking and {...H-C-C-F}(2) dimer synthons, and in vitro acetyl cholinesterase inhibition activity of phenoxy pendant isatins - Mehreen_2022_RSC.Adv_12_1788
Author(s) : Mehreen S , Ullah A , Nadeem H , Dege N , Naseer MM
Ref : RSC Adv , 12 :1788 , 2022
Abstract : A series of novel phenoxy pendant isatins PI1-12 have been synthesized in excellent yields by a simple nucleophilic substitution reaction involving isatins and 1-(2-bromoethoxy)-4-substituted benzenes, and characterized by their FT-IR, (1)H NMR, (13)C NMR and GC-MS data, and in the case of PI4 by its single crystal X-ray analysis. The solid-state structure of PI4 showed an intriguing and unique 1D-supramolecular chain-based self-assembled structure, the driving force of which is mainly the strong antiparallel Pi...Pi stacking and {...H-C-C-F}(2) dimer synthons. This compound not only highlights the potential of the isatin moiety in forming strong antiparallel Pi...Pi stacking interactions but also provides a platform to have considerable insight into the nature, strength and directionality of much debated Pi-Pi and C-H...F-C interactions. The in vitro biological studies revealed that three phenoxy pendant isatins PI1, PI2 and PI4 are highly potent inhibitors of acetylcholinesterase enzyme with IC(50) values of 0.52 +/- 0.073 microg ml(-1), 0.72 +/- 0.012 microg ml(-1) and 0.68 +/- 0.011 microg ml(-1), respectively, showing comparable activity to the standard drug, donepezil (IC(50) = 0.73 +/- 0.015 microg ml(-1)). A simple and efficient synthesis of phenoxy pendant isatins PI1-12 from inexpensive and commercially available starting materials, and their high potential of acetyl cholinesterase inhibition provide an attractive opportunity to find more effective medication for Alzheimer's disease (AD).
ESTHER : Mehreen_2022_RSC.Adv_12_1788
PubMedSearch : Mehreen_2022_RSC.Adv_12_1788
PubMedID: 35425213

Title : Synthesis, structure and acetylcholinesterase inhibition activity of new diarylpyrazoles - Zia_2022_Bioorg.Chem_121_105658
Author(s) : Zia M , Hameed S , Nadeem H , Kharl AA , Dege N , Paracha RZ , Arshad I , Naseer MM
Ref : Bioorg Chem , 121 :105658 , 2022
Abstract : A variety of diarylpyrazole derivatives III-VI were synthesized and structurally characterized using FTIR, (1)H and (13)C NMR spectroscopy, and in case of compound VIb by X-ray single crystal analysis. The in vitro biological studies revealed that seven of the diarylpyrazole derivatives IIIa, IIIb, IIId, IIIe, IVa, IVb and IVd are highly potent inhibitors of acetylcholinesterase enzyme with IC(50) values of 0.48 +/- 0.092 microg/mL, 0.45 +/- 0.093 microg/mL, 0.30 +/- 0.014 microg/mL, 0.59 +/- 0.072 microg/mL, 0.29 +/- 0.084 microg/mL, 0.56 +/- 0.010 microg/mL and 0.28 +/- 0.096 microg/mL, respectively. All these seven products were more potent than the standard drug, donepezil (IC(50) = 0.73 +/- 0.015 microg/mL), while compounds IIIc (0.67 +/- 0.099 microg/ml) and VIa (0.66 +/- 0.069 microg/ml) are almost equipotent to the donepezil. Particularly, compounds IVa and IVd are highly active acetylcholinesterase enzyme inhibitors, demonstrating more than two-fold inhibitory activity than the reference inhibitor. Molecular docking studies were carried out to identify the possible binding modes of the diarylpyrazoles within the active pocket of the enzymes. The docking interactions of the synthesized compounds with acetylcholinesterase also provided high docking scores. These results clearly indicate the potential of these compound as powerful lead molecules for further investigations.
ESTHER : Zia_2022_Bioorg.Chem_121_105658
PubMedSearch : Zia_2022_Bioorg.Chem_121_105658
PubMedID: 35182888